Sensor-based phrenic nerve stimulation detection

ABSTRACT

A method and device for detecting phrenic nerve stimulation (PNS) in, or using, a cardiac medical device. A test signal sensitive to contraction of a diaphragm of a patient may be sensed and signal artifacts of the test signal within each of a first window of the test signal prior to a predetermined cardiac signal and a second window of the test signal subsequent to the predetermined cardiac signal may be determined. The PNS beat criteria may be evaluated, for example, using the test signal, which may be a heart sounds signal.

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 62/595,854 filed on Dec. 7, 2017, which isincorporated by reference in its entirety.

A wide variety of implantable medical devices for delivering a therapyor monitoring a physiologic condition have been clinically implanted orproposed for clinical implantation in patients. In some cases,implantable medical devices (IMD) deliver electrical stimulation therapyand/or monitor physiological signals via one or more electrodes orsensor elements, which may be included as part of one or more elongatedimplantable medical leads. The implantable medical leads may beconfigured to allow one or more electrodes and/or sensors to bepositioned at desired locations for sensing and/or delivery ofstimulation. For example, electrodes or sensors are positioned at adistal portion of the lead and a connector is positioned at a proximalportion of the lead and coupled to an implantable medical devicehousing, which may contain electronic circuitry such as stimulationgeneration and/or sensing circuitry.

For example, implantable medical devices, such as cardiac pacemakers orimplantable cardioverter defibrillators, provide therapeutic stimulationto the heart by delivering electrical therapy signals, such as pulsesfor pacing, or shocks for cardioversion or defibrillation, viaelectrodes of one or more implantable leads. In some cases, such animplantable medical device senses for intrinsic depolarizations of theheart, and controls the delivery of such signals to the heart based onthe sensing. Upon detection of an abnormal rhythm, such as bradycardia,tachycardia or fibrillation, for example, an appropriate electricalsignal or signals may be delivered to restore the normal rhythm. Forexample, in some cases, an implantable medical device delivers pacing,cardioversion, or defibrillation signals to the heart of the patientupon detecting ventricular tachycardia, and delivers defibrillationelectrical signals to a patient's heart upon detecting ventricularfibrillation. Pacing signals typically have a lower energy than thecardioversion or defibrillation signals.

Pacing signals, cardioversion signals and defibrillation signals mayaffect tissue and nerves outside of the target tissue. For example, apacing pulse applied to the left ventricle may also result in unintendedphrenic nerve stimulation (PNS). In other examples, an electrical leadmay be placed proximate to the phrenic nerve and provide stimulationdesigned to stimulate the phrenic nerve. During cardiac stimulation, PNSmay cause unpleasant side effects for a patient, such as hiccups,dyspnea, uncomfortable muscle twitching and general malaise. PNS mayalso decrease the hemodynamic response to cardiac resynchronizationtherapy (CRT), or generally impair the hemodynamic performance of theheart, in the patient. When implanting a pacemaker, including leadplacement, and setting pacing parameters (e.g., choosing the strength ofstimulus), a physician or other clinician may attempt to detect andavoid PNS. In other instances, PNS may be provided as an additionaltherapy option for certain patients with a respiratory disorder.

Phrenic nerve stimulation (PNS) during left ventricular (LV) pacing forcardiac resynchronization therapy (CRT) may occur when the electrodesare near the phrenic nerve, leading to contraction of the diaphragm andpatient discomfort. The development of quadripolar LV leads has reducedthe rate of PNS complications requiring invasive LV lead repositioningor discontinuation of CRT, but PNS is still commonly encountered duringimplant and at patient follow-up, requiring either surgical interventionor reprogramming to resolve.

SUMMARY

In general, the disclosure is directed to detection of phrenic nervestimulation (PNS) using a heart sounds sensor in a cardiac medicaldevice. In some examples, pacing-induced phrenic nerve stimulation isdetected using the techniques described herein. In some examples,asymptomatic phrenic nerve stimulation is detected. In some examples,intentional, e.g., therapeutic, PNS is detected using the techniquesdescribed herein, e.g., to evaluate whether PNS has been achieved or theefficacy of PNS.

In one example, the disclosure is directed to a method of detectingphrenic nerve stimulation (PNS) in a cardiac medical device thatincludes sensing a test signal, the test signal being sensitive tocontraction of a diaphragm of a patient; determining signal artifacts ofthe test signal within each of a first window of the test signal priorto a predetermined cardiac signal and a second window of the test signalsubsequent to the predetermined cardiac signal; determining, in responseto signal artifacts of the test signal within the first window and thesecond window, whether PNS beat criteria have been satisfied;determining, in response to the PNS beat criteria being satisfied,whether PNS episode criteria have been satisfied; and detecting a PNSepisode in response to the PNS episode criteria being satisfied.

In another example, the disclosure is directed to a cardiac medicaldevice, comprising: a first sensor configured to sense a test signal,the test signal being sensitive to contraction of a diaphragm of apatient; a second sensor to a predetermined cardiac signal; and aprocessor configured to determine signal artifacts of the test signalwithin each of a first window of the test signal prior to apredetermined cardiac signal and a second window of the test signalsubsequent to the predetermined cardiac signal, determine, in responseto signal artifacts of the test signal within the first window and thesecond window, whether PNS beat criteria have been satisfied, determine,in response to the PNS beat criteria being satisfied, whether PNSepisode criteria have been satisfied, and detect.

In another example, the disclosure is directed to a non-transitorycomputer readable medium storing instructions which cause a cardiacmedical device to perform a method comprising: sensing a test signal,the test signal being sensitive to contraction of a diaphragm of apatient; determining signal artifacts of the test signal within each ofa first window of the test signal prior to a predetermined cardiacsignal and a second window of the test signal subsequent to thepredetermined cardiac signal; determining, in response to signalartifacts of the test signal within the first window and the secondwindow, whether PNS beat criteria have been satisfied; determining, inresponse to the PNS beat criteria being satisfied, whether PNS episodecriteria have been satisfied; and detecting a PNS episode in response tothe PNS episode criteria being satisfied.

These and other aspects of the present disclosure will be apparent fromthe detailed description below. In no event, however, should the abovesummaries be construed as limitations on the claimed subject matter,which subject matter is defined solely by the attached claims, as may beamended during prosecution.

BRIEF DESCRIPTION OF THE DRAWINGS

Throughout the specification, reference is made to the appendeddrawings, where like reference numerals designate like elements, andwherein:

FIG. 1 is a conceptual diagram illustrating an example system thatdetects phrenic nerve stimulation, consistent with an example of thepresent disclosure.

FIG. 2 is a conceptual diagram illustrating the implantable medicaldevice (IMD) and leads of the system shown in FIG. 1 in greater detail.

FIG. 3 is a block diagram illustrating an example configuration of theIMD of FIG. 1. FIG. 4 is a conceptual diagram illustrating an examplesystem that delivers phrenic nerve stimulation, consistent with anexample of the present disclosure.

FIG. 5 is a block diagram illustrating an example system that includesan external device, such as a server, and one or more computing devicesthat are coupled to the IMD and programmer shown in FIG. 1 via anetwork.

FIG. 6 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure.

FIG. 7 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure.

FIG. 8 is a graphical representation of determining of acousticartifacts of a heart sound signal for determining the presence ofphrenic nerve stimulation in a medical device, according to an exampleof the present disclosure.

FIG. 9 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure.

FIG. 10 is a flowchart of a method of determining the presence ofphrenic nerve stimulation in a medical device, according to an exampleof the present disclosure.

DETAILED DESCRIPTION

The techniques described in this disclosure may allow a medical deviceto automatically detect the presence of phrenic nerve stimulation. Insome examples, the phrenic nerve stimulation is an unintended sideeffect of electrical stimulation applied to a patient's heart. In otherexamples, the detected phrenic nerve stimulation may be purposeful. Forexample, phrenic nerve stimulation may be used to treat neurologicaldisorders affecting mechanical ventilation. In various examples, thedetection of phrenic nerve stimulation occurs in response to anactivation event. The activation event may be a change in the electricalstimulation applied to the patient's heart. In other examples, theactivation event may be a posture or activity level of the patientdetected by a posture or activity sensor. For example, an activationevent may be an indication that the patient is lying down. In otherexamples, the activation event may be the detection of low activity ofthe patient. In some examples, the activation event may be the detectionof combination of factors. For example, an activation event may be onthe occurrence of a particular posture or activity in conjunction with achange in the electrical stimulation. In other examples, the activationevent may be based on time. For example, an activation event may be thepassage of predetermined amount of time since the previous phrenic nervedetection sequence. In still other examples, the activation event may beon the occurrence of a particular time of day. In another example, thedetection of phrenic nerve stimulation may be initiated through input ata user interface of a device external to the medical device, such asduring implant of the medical device, post-implant, or during an officefollow-up visit by the patient either remotely or in office, forexample. In another example, the medical device may continuously andambulatorily analyze heart sounds signals for detection of phrenic nervewithout the use of an activation event.

Heart sounds are associated with mechanical vibrations from activity ofa patient's heart and the flow of blood through the heart. Heart soundsrecur with each cardiac cycle and are separated and classified accordingto the activity associated with the vibration. As used herein, the termheart sound refers to a feature of a heart sound signal, such as the S1,S2, S3, or S4 heart sounds. There may be multiple heart sounds, e.g.,each of an S1, S2, S3 and S4 heart sound, for any given cardiac cycle orheartbeat. The first heart sound (S1) is the vibrational sound made bythe heart during tensing of the mitral valve. The second heart sound(S2)is related to aortic and pulmonic valve closure. The third heartsound (S3) and fourth heart sound (S4) are related to filling of theleft ventricle during diastole. A heart sound sensor produces anelectrical signal which is representative of mechanical activity of apatient's heart. An example of a heart sound sensor includes anaccelerometer or microphone. An approach for measuring heart sounds canbe found in Seijko et al., “Method and Apparatus for Monitoring ofDiastolic Hemodynamics,” U.S. Pat. No. 7,115,096, filed on Dec. 30,2002, which is incorporated herein by reference in its entirety. Theevoked response parameter may include at least one of a measuredamplitude of a heart sound associated with evoked response, a time ofoccurrence of a heart sound associated with evoked response, and a powerof a heart sound associated with the evoked response.

In some examples, the medical device may classify a heartbeat or cardiaccycle as normal or abnormal based on the classifications for one or moreheart sounds detected during the heart beat or cardiac cycle. In suchexamples, the medical device may confirm that a cardiac rhythm istreatable when one or more heart beats are classified as abnormal, orwithhold therapy when one or more heart beats are classified as normal.In other examples, the heart sound signal may include signalsrepresenting other acoustic occurrences including, for example,diaphragm movement in response to phrenic nerve stimulation.

Pacing-induced phrenic nerve stimulation, both symptomatic andasymptomatic, may cause unpleasant symptoms and decreased hemodynamicperformance for the patient. In various examples consistent with thepresent disclosure, phrenic nerve stimulation may be both detected, andin response to the detection, avoided in the future.

Pacing-induced phrenic nerve stimulation is particularly of concern whenpacing is provided by a left-ventricular lead, such as aleft-ventricular quadrapolar lead. This is because a left-ventricularlead may position one or more electrodes in close proximity to the leftphrenic nerve. A physician may desire to program the IMD to providecardiac resynchronization therapy, including left-ventricular pacing,that provides heart function as close to normal while avoiding capturingone or more phrenic nerves with the applied pulses.

In some examples, the disclosure is directed to detecting pacing-inducedPNS using a PNS test signal, such as a heart sounds signal, or anaccelerometer signal, for example, and in response, reprogramming theIMD to provide CRT in a manner that does not capture the phrenic nerve.In some examples, reprogramming the IMD includes changing one or morepacing vectors to avoid phrenic nerve stimulation. In some examples,reprogramming the IMD includes modifying various pacing parameters suchas pulse strength to avoid phrenic nerve stimulation, with or withoutchanging the pacing vectors. In some examples, modification of the pulsestrength is first attempted and, if phrenic nerve stimulation is notavoided without compromising cardiac capture, modification of the pacingvector is attempted. The determination of new pulse strength or pacingvector may be made based on information extracted from the PNS testsignal. This is possible because sensors such as activity/posturesensors or heart sound sensors can detect diaphragmatic muscularmovement caused by both symptomatic and asymptomatic PNS in the form ofa motion artifact or sound artifact, respectively.

As discussed in more detail below with respect to the various figures,both symptomatic and asymptomatic PNS may be detected using a PNS testsignal, such as an accelerometer signal, or an acoustic signal. Invarious examples, IMD is not continuously monitoring the PNS test signalfor PNS. Instead, a detection sequence may be initiated at a given timeof day, for example. This allows the IMD to save battery power and toperform other functions using the same sensors and processors at othertimes. In some examples, PNS detection is initiated at times that PNS ismost likely to be detected. For example, a PNS detection sequence may beinitiated when a patient is lying on his or her left side. In instanceswhere a left-ventricular lead is used to deliver cardiac pacing, phrenicnerve stimulation may occur when the patient is on his or her left side,but not when the patient is in other positions. In another example, aPNS detection sequence may be initiated by a clinician using amonitoring device at a clinic.

For pacing induced PNS, the IMD, or another device that communicateswith the IMD, may determine signal artifacts of the sensed PNS testsignal just before and after a predetermined timing signal, such as a150 ms time delay, for example, or just before and after a predeterminedcardiac signal, such as a ventricular pace (Vp) beat, and an atrialsense (As) beat, or an atrial pace (Ap) beat. The device determineswhether PNS beat criteria have been met based on the determined signalartifacts before and after the predetermined timing signal, or based onthe determined signal artifacts before and after the predeterminedcardiac signal. If the PNS beat criteria are not satisfied, the beat isdetermined not to be a PNS beat and the process resumes for the nextbeat. On the other hand, if the PNS beat criteria are satisfied, the IMDdetermines that a PNS episode is occurring. For example, as describedbelow, PNS detection of the present disclosure may evaluate presence orabsence of PNS on a beat-by-beat basis by detecting an acoustic artifactof a heart sounds signal that occurs after a left ventricular (LV) pace(Vp). While the determination of signal artifacts is described below inreference to signal artifacts occurring before and after a predeterminedcardiac signal, it is understood that the determination of signalartifacts may be performed in reference to a timing signal, such as a150 ms time delay, for example.

The analyzed heart sounds signal data may be digitized by a 16-bit ADCwith ±64 mV range sampled at 256 Hz, and bandpass filtered. The absolutevalue of the filtered heart sounds signal (|FHS|) is determined and apredetermined number of beats are evaluated for PNS at a user selectablevoltage and/or polarity. In one example, in order to ensure that theevaluation is completed in less than 3 minutes at an estimated heartrate of 60 bpm for 16 vectors (11×16×1000 ms cycle length=176 s), up to11 beats are evaluated for PNS at the user selectable voltage output.For each PNS test beat, a PNS window that includes a PreVp window and aPostVp window, and a noise window of the heart sounds signal may bedetermined for use in evaluating and detecting whether PNS is present.In one example, the PreVp window may include 25 samples before and up tothe Vp beat (98 ms), the PostVp window may occur 7 to 21 samples (27 to82 ms) after the Vp beat for a left-sided device implant, or 20 to 32 ms(78 to 125 ms) after the Vp beat for a right-sided device implant, andthe noise window may occur 7 to 80 samples (27 to 313 ms) after the Vpbeat.

Signal features of the heart sounds signal, such as one or more ofmaximum, minimum, range, mean, sum and absolute difference of the signalare calculated within each window. Absolute difference is analogous tostandard deviation (SD) and is calculated by subtracting the mean from asignal, summing the absolute value of the resulting time series anddividing by the length of the signal. Heart sound signal features withinthe noise window are first evaluated for each beat to detect ordetermine whether the beat is associated with noise, and if noise is notdetected for the beat, the heart sound signal features within the PNSwindow are evaluated for the beat to detect or determine whether thebeat is associated with presence of PNS. If the beat is neither a noisebeat nor a PNS beat, the beat is classified as a non-PNS beat, and theprocess continues for the next beat identified by the heart soundssignal until a predetermined number of beats have been evaluated, or apredetermined time period has expired. On the other hand, if the beat isnot identified as being a noise beat but is identified as being a PNSbeat, the beat is classified as a PNS beat. In either case, i.e., thecurrent beat being a PNS beat or a non-PNS beat, the process continuesfor the next beat until a predetermined number of beats have beenevaluated, a predetermined time period has expired, or a PNS episode isdetected based on a predetermined sequence of beats being identified asPNS beats.

In an attempt to avoid PNS when setting pacing parameters, the IMD maystep up the pacing pulse amplitude and/or width from the minimal pacingcapture threshold to the maximum output of the IMD. In some examples,the IMD may stop the stepping up process when PNS is detected. In someexamples where PNS detection is implemented after the pacing parametershave been set, the IMD steps down the amplitude of the pacing pulseafter an initial determination of PNS until PNS is no longer detected,so long as cardiac capture is maintained.

In some examples, it may be desirable to determine if a preferred orchosen pacing vector or modality will cause PNS for a specific patient.This may be done by first applying pacing stimulation at the maximumoutput of the stimulation generator to see if PNS is present or not. If

PNS is present, then the IMD may gradually step-down the pacing pulseamplitude until the minimal pacing amplitude that still causes PNS isdetermined (PNS threshold). If the PNS threshold is above the thresholdfor capturing the ventricle to provide adequate pacing, then the chosenpacing vector may still be used. If not, then another vector orelectrode configuration may be tested until one is found where a pacingpulse may be delivered that provides pacing capture without alsostimulating the phrenic nerve.

In some examples, once PNS is detected, the IMD, or another device thatcommunicates with the IMD, may modify the pacing parameters to providepacing that does not compromise the patient's hemodynamics whileavoiding PNS. In some examples, the heart sound signal is used to assessthe pacing parameters not only for PNS but for overall heart function.

In some examples, the method of detecting PNS, described below, may beperformed by another device that communicates with the IMD and enablesautomatic PNS detection using only a heart sound signal. The PNSdetection feature may therefore reduce the time required to evaluate PNSat implant and potentially reduce symptomatic PNS post-implant bydetecting indications not detected with manual PNS assessment, i.e.visually, by palpation, or under fluoroscopy, for example.

In some examples, phrenic nerve stimulation may be desired. For example,it may be desirable to provide PNS as a substitute for mechanicalventilation in patients with neurological disorders such as centralsleep apnea. In such examples, the amount of stimulation applied may bedifferent every few pulses in order to simulate normal breathingpatterns. PNS detection using heart sounds may be used to confirm theeffectiveness of the attempted phrenic nerve stimulation.

FIG. 1 is a conceptual diagram illustrating an example system 10 thatmay detect phrenic nerve stimulation. In some examples, system 10monitors both cardiac electrical activity and heart sounds-basedsignals. In some examples, system 10 provides stimulation to the cardiactissue based on a set of parameters, and monitors a signalrepresentative of cardiac electrical activity, e.g., an electrogram(EGM), and a heart sounds signal. Based at least on the heart soundssignal, system 10 determines whether the cardiac stimulation at thepresent stimulation parameters is causing unwanted phrenic nervestimulation.

System 10 includes implantable medical device (IMD) 16, which isconnected to leads 18, 20 and 22 and is optionally communicativelycoupled to programmer 24. IMD 16 senses electrical signals attendant tothe depolarization and repolarization of heart 12, e.g., a cardiac EGM,via electrodes on one or more leads 18, 20 and 22 or the housing of IMD16. In some examples, IMD 16 also delivers cardiac therapy in the formof electrical signals to heart 12 via electrodes located on one or moreleads 18, 20 and 22 or a housing of IMD 16. The cardiac therapy may bepacing, cardioversion and/or defibrillation pulses. The IMD 16 may alsoprovide respiratory induction therapy. The respiratory induction therapyincludes electrical stimulation to one or more phrenic nerves 36 and 38via electrodes located on one or more of leads 18, 20 and 22, otherleads not illustrated in FIG. 1, or a housing of IMD 16. bIn someexamples, the electrodes used to stimulate phrenic nerves 36 and 38 maybe used for both cardiac and phrenic nerve stimulation. IMD 16 alsoincludes one or more heart sound sensors (not shown in FIG. 1) used todetect the occurrence of phrenic nerve stimulation in patient 14. IMD 16may similarly include or be coupled to other sensors, such as one ormore accelerometers, for detecting other physiological parameters ofpatient 14, such as activity or posture.

In some examples, programmer 24 takes the form of a handheld computingdevice, computer workstation or networked computing device that includesa user interface for presenting information to and receiving input froma user. A user, such as a physician, technician, surgeon,electro-physiologist, or other clinician, may interact with programmer24 to retrieve physiological or diagnostic information from IMD 16. Auser may also interact with programmer 24 to program IMD 16, e.g.,select values for operational parameters of the IMD or initiate aphrenic nerve stimulation detection sequence.

IMD 16 and programmer 24 may communicate via wireless communicationusing any techniques known in the art. Examples of communicationtechniques may include, for example, low frequency or radiofrequency(RF) telemetry. Other techniques are also contemplated. In someexamples, programmer 24 may include a programming head that may beplaced proximate to the patient's body near the IMD 16 implant site inorder to improve the quality or security of communication between IMD 16and programmer 24. In other examples, programmer 24 may be locatedremotely from IMD 16, and communicate with IMD 16 via a network.

Leads 18, 20, 22 extend into the heart 12 of patient 14 to senseelectrical activity of heart 12 and/or deliver electrical stimulation toheart 12. The leads may also deliver electrical stimulation to phrenicnerve 38. In the example shown in FIG. 1, right ventricular (RV) lead 18extends through one or more veins (not shown), the superior vena cava(not shown), and right atrium 26, and into right ventricle 28. Leftventricular (LV) coronary sinus lead 20 extends through one or moreveins, the vena cava, right atrium 26, and into the coronary sinus 30 toa region adjacent to the free wall of left ventricle 32 of heart 12.Right atrial (RA) lead 22 extends through one or more veins and the venacava, and into the right atrium 26 of heart 12. In some examples, RAlead 22 may be used to stimulate right phrenic nerve 36. I n someexamples, LV coronary sinus lead 20 may be used to stimulate leftphrenic nerve 38.

Techniques for detecting stimulation of one or more of phrenic nerves 36and 38 are primarily described herein as being performed by IMD 16,e.g., by processing circuitry of a processor of IMD 16. In otherexamples, some or all of the functions ascribed to IMD 16 or a processorthereof may be performed by one or more other devices such as programmer24, or a processor thereof. For example, IMD 16 may process cardiacand/or heart sound signals to determine whether therapy should continueto be delivered based on current parameters, or whether adjustments tothe parameters should be made, and control the parameters used by IMD 16to deliver the therapy. Alternatively, programmer 24 may process cardiacand/or heart sound signals received from IMD 16 to determine whethertherapy should continue to be delivered based on current parameters orwhether adjustments to the parameters should be made, and controlaccording to what parameters IMD 16 delivers the therapy. Furthermore,although described herein with respect to an IMD, in other examples, thetechniques described herein may be performed or implemented in anexternal medical device, which may be coupled to a patient viapercutaneous or transcutaneous leads. In some examples, variousfunctions of IMD 16 may be carried out by multiple IMDs in communicationwith one another.

FIG. 2 is a conceptual diagram illustrating IMD 16 and leads 18, 20 and22 of system 10 in greater detail. In the illustrated example, bipolarelectrodes 40 and 42 are located adjacent to a distal end of lead 18. Inaddition, bipolar electrodes 44 and 46 are located adjacent to a distalend of lead 20, and bipolar electrodes 48 and 50 are located adjacent toa distal end of lead 22.

In alternative examples, not shown in FIG. 2, one or more of leads 12,20 and 22, such as left-ventricular lead 20, may include quadrapoleelectrodes located adjacent to a distal end of the lead.

In the illustrated example, electrodes 40, 44 and 48 take the form ofring electrodes, and electrodes 42, 46 and 50 may take the form ofextendable helix tip electrodes mounted retractably within insulativeelectrode heads 52, 54 and 56, respectively. Leads 18, 20, 22 alsoinclude elongated electrodes 62, 64, 66, respectively, which may takethe form of a coil. In some examples, each of electrodes, 40, 42, 44,46, 48, 50, 62, 64 and 66 is electrically coupled to a respectiveconductor within the lead body of its associated lead 18, 20, 22, andthereby coupled to circuitry within IMD 16.

In some examples, IMD 16 includes one or more housing electrodes, suchas housing electrode 4 illustrated in FIG. 2, which may be formedintegrally with an outer surface of hermetically-sealed housing 8 of IMD16 or otherwise coupled to housing 8. In some examples, housingelectrode 4 is defined by an uninsulated portion of an outward facingportion of housing 8 of IMD 16. Other divisions between insulated anduninsulated portions of housing 8 may be employed to define two or morehousing electrodes. In some examples, a housing electrode comprisessubstantially all of housing 8.

As described in further detail with reference to FIG. 3, housing 8encloses a signal generator that generates therapeutic stimulation, suchas cardiac pacing, cardioversion and defibrillation pulses, as well as asensing module for sensing electrical signals attendant to thedepolarization and repolarization of heart 12. IMD 16 may also include aheart sounds sensor that monitors acoustic noises including heart soundsand sounds resulting from phrenic nerve stimulation, for example. Theheart sounds sensor may be, for example, an accelerometer or amicrophone. The heart sounds sensor may be enclosed within housing 8.Alternatively, the heart sounds sensor may be integrally formed with orcarried on an outer surface of housing 8, carried on or within a leadcoupled to IMD 16, such as one or more leads 18, 20 and 22, or be aseparate, remote sensor that wirelessly communicates with IMD 16,programmer 24 or any other device described herein.

IMD 16 senses electrical signals attendant to the depolarization andrepolarization of heart 12 via electrodes 4, 40, 42, 44, 46, 48, 50, 62,64 and 66. IMD 16 may sense such electrical signals via any bipolarcombination of electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66.

Furthermore, any of the electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66may be used for unipolar sensing in combination with housing electrode4.

In some examples, IMD 16 delivers stimulating pulses via bipolarcombinations of electrodes chosen based on EGM signals and/or heartsound signals as analyzed by a signal analyzer within IMD. For example,bipolar combinations of electrodes 40, 42, 44, 46, 48, and 50 are usedto produce depolarization of cardiac tissue of heart 12. In addition,phrenic nerve stimulation pulses may be delivered by various electrodesused to provide cardiac stimulation, and which electrodes may be chosento deliver phrenic nerve stimulation based on the location of theelectrodes. In some examples, IMD 16 delivers stimulation to eithercardiac tissue or the phrenic nerve via any of electrodes 40, 42, 44,46, 48 and 50 in combination with housing electrode 4 in a unipolarconfiguration. In some examples, the choice of electrodes deliveringcardiac and phrenic nerve electrical stimulation may be based on defaultsettings. Furthermore, IMD may deliver cardioversion or defibrillationpulses to heart 12 or pulses to phrenic nerves 36 and 38 via anycombination of elongated electrodes 62, 64, 66 and housing electrode 4.

The illustrated numbers and configurations of leads 18, 20 and 22 andelectrodes are merely examples. Other configurations, i.e., numbers andpositions of leads and electrodes, are possible. In some examples,system 10 may include an additional lead or lead segment having one ormore electrodes positioned at different locations in the cardiovascularsystem for sensing and/or delivering therapy to patient 14. For example,instead of or in addition to intracardiac leads 18, 20 and 22, system 10may include one or more epicardial or subcutaneous leads not positionedwithin the heart. For example, a lead may be positioned to provide oneor more electrodes in proximity to or in contact with phrenic nerve 36or phrenic nerve 38. As another example, system 10 may include anadditional lead that carries a heart sound sensor positioned such thatsignals generated by the heart sounds sensor include informationregarding a patient's respiratory activity including, for example,inspiration and expiration.

FIG. 3 is a block diagram illustrating an example configuration of IMD16. In the illustrated example, IMD 16 includes a processor 70, memory72, signal generator 74, sensing module 76, telemetry module 78, asignal analyzer 80, a heart sounds sensor 82, and an activity/posturesensor 84. Memory 72 includes computer-readable instructions that, whenexecuted by processing circuitry of processor 70, cause IMD 16 andprocessor 70 to perform various functions attributed to IMD 16 andprocessor 70 herein. Memory 72 may include any volatile, non-volatile,magnetic, optical, or electrical media, such as a random access memory(RAM), read-only memory (ROM), non-volatile RAM (NVRAM),electrically-erasable programmable ROM (EEPROM), flash memory, or anyother digital or analog media.

Processor 70 may include any one or more of a microprocessor, acontroller, a digital signal processor (DSP), an application specificintegrated circuit (ASIC), a field-programmable gate array (FPGA), orequivalent discrete or analog logic circuitry. In some examples,processor 70 may include multiple components, such as any combination ofone or more microprocessors, one or more controllers, one or more DSPs,one or more ASICs, or one or more FPGAs, as well as other discrete orintegrated logic circuitry. The functions attributed to processor 70herein may be embodied as software, firmware, hardware or anycombination thereof. Generally, processor 70 controls signal generator74 to deliver stimulation therapy to heart 12 of patient 14 according toa selected one or more of therapy programs or parameters, which may bestored in memory 72. As an example, processor 70 may control signalgenerator 74 to deliver electrical pulses with the amplitudes, pulsewidths, frequency, or electrode polarities specified by the selected oneor more therapy programs. The therapy programs may be selected by theprocessor 70 based on information from the signal analyzer 80.

Signal generator 74 is configured to generate and deliver electricalstimulation therapy to patient 12. As shown in FIG. 3, signal generator74 is electrically coupled to electrodes 4, 40, 42, 44, 46, 48, 50, 62,64 and 66, e.g., via conductors of the respective leads 18, 20, and 22and, in the case of housing electrode 4, within housing 8. For example,signal generator 74 may deliver stimulating pulses to phrenic nerves 36and 38 via at least two of electrodes 4, 40, 42, 44, 46, 48, 50, 62, 64and 66. In addition, in some examples, signal generator 74 may deliverpacing pulses, defibrillation shocks or cardioversion shocks to heart 12via at least two of electrodes 4, 40, 42, 44, 46, 48, 50, 62, 64 and 66.In some examples, signal generator 74 delivers stimulation in the formof signals other than pulses such as sine waves, square waves, or othersubstantially continuous time signals.

Signal generator 74 may include a switch module (not shown) andprocessor 70 may use the switch module to select, e.g., via adata/address bus, which of the available electrodes are used to deliverthe electrical stimulation. The switch module may include a switcharray, switch matrix, multiplexer, or any other type of switching devicesuitable to selectively couple stimulation energy to selectedelectrodes. Electrical sensing module 76 monitors electrical cardiacsignals from any combination of electrodes 4, 40, 42, 44, 46 48, 50, 62,64, and 66. Sensing module 76 may also include a switch module whichprocessor 70 controls to select which of the available electrodes areused to sense the heart activity, depending upon which electrodecombination is used in the current sensing configuration.

Sensing module 76 may include one or more detection channels, each ofwhich may comprise an amplifier. The detection channels may be used tosense the cardiac signals. Some detection channels may detect events,such as R-waves or P-waves, and provide indications of the occurrencesof such events to processor 70 and/or signal analyzer 80. One or moreother detection channels may provide the signals to an analog-to-digitalconverter, for conversion into a digital signal for processing oranalysis by processor 70 or signal analyzer 80.

For example, sensing module 76 may comprise one or more narrow bandchannels, each of which may include a narrow band filteredsense-amplifier that compares the detected signal to a threshold. If thefiltered and amplified signal is greater than the threshold, the narrowband channel indicates that a certain electrical cardiac event, e.g.,depolarization, has occurred. Processor 70 then uses that detection inmeasuring frequencies of the sensed events. Signal analyzer 80 may usethe detection in connection with sensed heart sounds to determine one ormore cardiac metrics.

In one example, at least one narrow band channel may include an R-waveor P-wave amplifier. In some examples, the R-wave and P-wave amplifiersmay take the form of an automatic gain controlled amplifier thatprovides an adjustable sensing threshold as a function of the measuredR-wave or P-wave amplitude. Examples of R-wave and P-wave amplifiers aredescribed in U.S. Pat. No. 5,117,824 to Keimel et al., which issued onJun. 2, 1992 and is entitled, “APPARATUS FOR MONITORING ELECTRICALPHYSIOLOGIC SIGNALS,” and is incorporated herein by reference in itsentirety.

In some examples, sensing module 76 includes a wide band channel whichmay comprise an amplifier with a relatively wider pass band than thenarrow band channels. Signals from the electrodes that are selected forcoupling to the wide-band amplifier may be converted to multi-bitdigital signals by an analog-to-digital converter (ADC) provided by, forexample, sensing module 76, processor 70, or signal analyzer 80.Processor 70 may analyze the digitized version of signals from the wideband channel. Processor 70 may employ digital signal analysis techniquesto characterize the digitized signals from the wide band channel to, forexample, detect and classify the patient's heart rhythm. In someexamples, the signal analyzer 80 employs digital signal analysistechniques to characterize the digitized signals from the wide bandchannel. The digitized signals may be used in conjunction with heartsound signals to determine if phrenic nerve stimulation has occurred.

Processor 70 may initiate a phrenic nerve stimulation detection sequencein response to detecting an activation event. In some examples,processor 70 may receive an activation signal from programmer 24 viatelemetry module 78, which may be the activation event, beforeinitiating phrenic nerve stimulation detection. In some examples, theactivation event may be one or more of an activity/posture detected viaactivity posture sensor 84, signal analyzer 80, memory 72, and sensingmodule 76. In some examples, processor 70 may initiate phrenic nervestimulation detection at a given time. For example, memory 72 mayprovide a program to processor 70 wherein phrenic nerve stimulationdetection occurs every day at a predetermined time. In such cases theactivation event is the time of day. In other examples, processor 70 mayinitiate phrenic nerve stimulation detection during a predetermined timerange when predefined parameters are met. For example, processor 70 mayinitiate phrenic nerve stimulation detection between 10 p.m. and 5 a.m.when an activation event, such as activity/posture sensor 84 indicatingthat patient 12 is lying down, occurs. In some specific examples,processor 70 may initiate phrenic nerve stimulation detection inresponse to an activation event such as an indication from theactivity/posture sensor 84 that patient 12 is lying on his or her leftside is received. In some examples, processor 70 may initiate a phrenicnerve stimulation detection sequence based on an activation event suchas one or more pacing parameters changing. In some examples, processor70 may initiate a phrenic nerve stimulation detection sequence inconjunction with a pacing parameter optimization process.

In the example in FIG. 3 (e.g., to detect the presence of phrenic nervestimulation), IMD 16 also includes heart sound sensor 82 and signalanalyzer 80. Heart sound sensor 82 generates an electrical signal basedon sensed acoustics or vibrations originating from heart movement anddiaphragm movement, for example. In some examples, heart sound sensor 82may comprise more than one sensor. For example, the heart sound sensormay include multiple individual sensors. In some examples, heart soundsensor 82 is an acoustic sensor, such as an accelerometer, microphone,or piezoelectric device. The acoustic sensor picks up sounds resultingfrom the activation of the diaphragm in addition to the heart soundsS1-S4.

In the illustrated example of FIG. 3, heart sounds sensor 82 is enclosedwithin housing 8 of IMD 16. In some examples, heart sounds sensor 82 maybe formed integrally with or on an outer surface of housing 8. In someexamples, heart sounds sensor 82 is located on one or more leads thatare coupled to IMD 16 or may be implemented in a remote sensor thatwirelessly communicates with IMD 16. In such cases, heart sounds sensor82 may be electrically or wirelessly coupled to circuitry containedwithin housing 8 of IMD 16. In some examples, a remote heart soundsensor 82 may be wirelessly connected to programmer 24.

Signal analyzer 80 receives the electrical signal generated by heartsounds sensor 82. In one example, signal analyzer 80 may process thesensor signal generated by heart sounds sensor 82 to detect occurrencesof phrenic nerve stimulation. In some examples, signal analyzer 80processes the heart sound sensor signal to generate an envelope signal,detect occurrences of phrenic nerve stimulation, detect other heartssounds, extract heart sound features from the detected heart soundsignal, and assess various cardiac metrics. The cardiac metrics mayprovide a method to assess the electrical-mechanical functioning of theheart 12. I n some examples, the detected heart sound features, boththose associated with phrenic nerve stimulation, and those associatedwith other heart activity, may be compared to values for each featurestored in memory 72. The heart sound features may then be classifiedbased on the deviation from the stored values. The heart sound featuresand/or their classifications may be used to determine whether phrenicnerve stimulation has occurred, and to assess the function of heart 12.

A heart sound based indication may be output from signal analyzer 80 toprocessor 70. In some examples, the heart sound features are output tothe processor 70. The processor 70 may determine whether phrenic nervestimulation has occurred based on the information received from signalanalyzer 80. In some examples, processor may adjust stimulation providedby signal generator 74 based on the heart sounds-based informationreceived.

In various examples one or more of the functions attributed to signalanalyzer 80 may be performed by processor 70. In some examples, signalanalyzer 80 may be implemented as hardware, software, or somecombination thereof. For example, the functions of signal analyzer 80described herein may be implemented in a software process executed byprocessor 70.

FIG. 4 is a conceptual diagram illustrating an example system 100 fordetecting phrenic nerve stimulation using heart sounds. The system 100includes IMD 16 that monitors heart sounds based signals and determinesif the phrenic nerve is being stimulated based on the heart sounds-basedsignal. In some examples IMD 16 may also monitor cardiac electricalactivity signals, e.g., EGM signals, and may provide cardiac tissuestimulation. In some examples, the detection of phrenic nervestimulation may trigger an optimization protocol for the pacingparameters used to provide the cardiac tissue stimulation. In someexamples, the system 100 detects the occurrence of phrenic nervestimulation and provides an indication of the phrenic nerve stimulationto a remote device, for example, programmer 24.

System 100 includes IMD 16, which is connected to leads 104, 106, 112and 114, and is optionally communicatively coupled to a programmer (notshown in FIG. 4). IMD 16 senses various signals attendant to activationof diaphragm 102 in response to electrical stimulation of phrenic nerves36 and 38. In some examples, leads 104 and 106 are positioned proximateto the phrenic nerves. The stimulation may be provided to phrenic nerves36 and 38 via electrodes 108 and 110. Leads 104 and 106 may beintracardiac leads including additional electrodes (not shown) providingcardiac stimulation, and leads 112 and 114 may be intracardiac leads,e.g., for providing cardiac stimulation. In some examples, electrodes108 and 110 may be cuff electrodes that at least partially surroundphrenic nerves 36 and 38, respectfully.

In some examples, IMD 16 senses electrical signals attendant to thedepolarization and repolarization of heart 12, e.g., a cardiac EGM, viaelectrodes on one or more of leads 104, 106, 112 and 114, or the housingof IMD 16. In some examples, IMD 16 delivers cardiac therapy in the formof electrical signals to heart 12 via electrodes located on one or moreof leads 104, 106, 112 and 114. IMD may also include, or be coupled to,other sensor such as one or more accelerometers for detecting otherphysiological parameters of a patient, such as activity or posture.

Techniques for monitoring stimulation of one or more of phrenic nerves36 and 38 are primarily described herein as being performed by IMD 16,e.g., by a processor of IMD 16. For example, IMD 16 may process heartsounds signals to determine whether the IMD 16 should continue todeliver based on current parameters, or whether adjustments to theparameters should be made. The processor in IMD 16 may also control theparameters used by 16 to deliver therapy. It is understood that, inanother example, the techniques of the present disclosure may also beperformed by another device that communicates with the IMD 16, such as aprogramming and/or monitoring device at a clinic.

FIG. 5 is a block diagram illustrating an example system that includesan external device, such as a server 206, and one or more computingdevices 212A-212N that are coupled to the IMD 16 and programmer 24 shownin FIG. 1 via a network 204. Network 204 may be generally used totransmit diagnostic information (e.g., the occurrence of phrenic nervestimulation) from an IMD 16 to a remote external computing device. Insome examples, the heart sounds and/or EGM signals may be transmitted toan external device for processing.

In some examples, the IMD 16 transmits information during predeterminedwindows of time. In some examples, the windows of transmission alignwith a window during which an activation event may result in theinitiation of a phrenic nerve detection sequence. In some examples,network 204 may also transmit information from IMD 16 regarding theactivation event that triggered the phrenic nerve stimulation to theremote external computing device.

In some examples, the information transmitted by IMD 16 may allow aclinician or other healthcare professional to monitor patient 14remotely. In some examples, IMD 16 may use its telemetry module 78 tocommunicate with programmer 24 via a first wireless connection, and tocommunicate with an access point 202 via a second wireless connection,e.g., at different times.

In the example of FIG. 5, access point 202, programmer 24, server 206,and computing devices 212A-212N are interconnected, and able tocommunicate with each other, through network 204. In some cases, one ormore of access point 202, programmer 24, server 206, and computingdevices 212A-212 N may be coupled to network 204 via one or morewireless connections. IMD 16, programmer 24, server 206, and computingdevices 212A-212N may each comprise one or more processors, such as oneor more microprocessors, DSPs, ASICs, FPGAs, programmable logiccircuitry, or the like, that may perform various functions andoperations, such as those described herein.

Access point 202 may comprise a device that connects to network 204 viaany of a variety of connections, such as telephone dial-up, digitalsubscriber line (DSL), or cable modem connections. In other examples,access point 202 may be coupled to network 204 through different formsof connections, including wired or wireless connections. In someexamples, access point 202 may be co-located with patient 14 and maycomprise one or more programming units and/or computing devices (e.g.,one or more monitoring units) that may perform various functions andoperations described herein. For example, access point 202 may include ahome-monitoring unit that is co-located with patient 14 and that maymonitor the activity of IMD 16. In some examples, server 206 orcomputing devices 212 may control or perform any of the variousfunctions or operations described herein, e.g., determine, based onheart sounds, whether the phrenic nerve is being stimulated.

In some cases, server 206 may be configured to provide a secure storagesite for archival of diagnostic information (e.g., occurrence of phrenicnerve stimulation and attendant circumstances such as pacing parameters)that has been collected and generated from IMD 16 and/or programmer 24.Network 204 may comprise a local area network, wide area network, orglobal network, such as the Internet. In some cases, programmer 24 orserver 206 may assemble PNS information in web pages or other documentsfor viewing by and trained professionals, such as clinicians, viaviewing terminals associated with computing devices 212. The system ofFIG.

5 may be implemented, in some aspects, with general network technologyand functionality similar to that provided by the Medtronic CareLink.®.Network developed by Medtronic, Inc., of Minneapolis, Minn.

In the example of FIG. 5, external server 206 may receive heart soundinformation from IMD 16 via network 204. Based on the heart soundinformation received, processor(s) 210 may perform one or more of thefunctions described herein with respect to signal analyzer 80 andprocessor 70. In some examples, an external device such as server 206 orcomputing devices 212 may provide an activation signal to IMD 16 vianetwork 204. In response to the activation signal, IMD 16 may initiate aphrenic nerve detection sequence consistent with one or more of themethods described below, for example. In some examples, heart soundsignals are transmitted to the external device that sent the activationsignal. The external device, such as server 206 processes the signalsusing the phrenic nerve detection features described below to determinewhether phrenic nerve stimulation has occurred.

FIG. 6 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure. As illustrated in FIG. 6, in order to determine thepresence of phrenic nerve stimulation, the device, such as IMD 16, forexample, or a device or monitoring system external to IMD 16, mayperform the determination on a beat-by-beat basis by sensing a PNS testsignal that is sensitive to contraction of a diaphragm of a patient,such as an acoustic signal or an accelerometer signal, for example,Block 300. The device determines signal artifacts of the sensed PNS testsignal which occur during a post cardiac signal window after apredetermined cardiac signal and a pre-cardiac signal window before thepredetermined cardiac signal, Block 302. Based on the determined signalartifacts of the PNS test signal, the device determines whether PNS beatcriteria have been met for the beat, Block 304, and if the PNS beatcriteria have been met for the beat, Yes in Block 304, the beat isidentified as a PNS beat, Block 306. On the other hand, if the PNS beatcriteria have not been met for the beat, No in Block 304, the beat isidentified as not being a PNS beat, Block 308, and the process isrepeated for the next beat, Block 310.

When the current beat is identified as being a PNS beat, Block 306, thedevice determines whether PNS episode criteria have been met, Block 312.If the PNS episode criteria have not been met, No in Block 312, theprocess is repeated for the next beat, Block 310. If the PNS episodecriteria have been met, Yes in Block 312, the device determines that aPNS episode is occurring, Block 314. In one example, PNS episodedetection criteria are determined to be met, Yes in Block 312, once aspecific number or sequence of PNS beats have been detected. Forexample, PNS detection episode criteria may be met if a predeterminednumber of consecutive beats, such as three beats for example, areidentified on a beat-by-beat basis as PNS beats. According to anotherexample, the PNS episode detection criteria may be met if PNS isdetected for every predetermined sequential beat for a total number ofbeats, such as for every third beat for three total beats, i.e.,beat(i), beat (i-3), beat (i-6), for example. Once the PNS episodedetection criteria are met and therefore a PNS episode is detected,Block 314, the device may generate an alert, adjust the pacing vectorfor delivery of the pacing therapy, or suspend delivery of the pacingtherapy. In one example, the device may suspend determining the presenceof PNS in response to the determination as to whether the PNS episodedetection criteria having been being determined for 11 consecutive beatswithout a PNS episode being detected.

Therefore, in the example of FIG. 6, PNS test signal features within thePNS window are evaluated for the beat to detect or determine whether thebeat is associated with presence of PNS. If the beat is not determinedto be a PNS beat, the beat is classified as a non-PNS beat, and theprocess continues for the next beat identified by the PNS test signaluntil a predetermined number of beats have been evaluated, or apredetermined time period has expired. On the other hand, if the beat isdetermined to be a PNS beat, the beat is classified as a PNS beat. Ineither case, i.e., the current beat being a PNS beat or not being a PNSbeat, the process continues for the next beat until either apredetermined number of beats have been evaluated, a predetermined timeperiod has expired, or a PNS episode is detected based on apredetermined number or sequence of beats being identified, on abeat-by-beat basis, as PNS beats.

FIG. 7 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure. In certain instances, it may be desirable to ensurethat the determination of a beat being a PNS beat does not occur as aresult of noise occurring in the PNS test signal. For example, asillustrated in FIG. 7, in order to determine the presence of phrenicnerve stimulation, the device may sense a PNS test signal that issensitive to contraction of a diaphragm of a patient, such as anacoustic signal or an accelerometer signal, Block 300. The devicedetermines, on a beat-by-beat basis, signal artifacts of the test signalfor each beat, Block 302, which occur during a noise window extendingover a period of time subsequent to the sensed predetermined cardiacsignal, in addition to a pre-cardiac signal window extending over aperiod of time prior to the sensed predetermined cardiac signal and apost-cardiac signal window extending a period of time subsequent to thesensed predetermined cardiac signal. Based on the determined signalartifacts of the noise window, the device determines whether PNS noisecriteria have been met, Block 303. If the PNS noise criteria have beenmet, Yes in Block 303, the beat is determined to be a noise beat, Block305, and the process is repeated for the next beat, Block 310. If thePNS noise criteria have not been met, No in Block 303, the devicedetermines whether PNS beat criteria have been met for the beat, Block304. If the PNS beat criteria have been met for the beat, Yes in Block304, the beat is identified as a PNS beat, Block 306. On the other hand,if the PNS beat criteria have not been met for the beat, No in Block304, the beat is identified as not being a PNS beat, Block 308, and theprocess is repeated for the next beat, Block 310.

Each time the current beat is both not identified as being a noise beatand identified as being a PNS beat, Block 306, the device determineswhether PNS episode criteria have been met, Block 312. If the PNSepisode criteria have not been met, No in Block 312, the process isrepeated for the next beat, Block 310. If the PNS episode criteria havebeen met, Yes in Block 312, the device determines that a PNS episode isoccurring, Block 314.

In this way, using only the PNS test signal, each beat is firstevaluated to determine whether the beat is a noise beat, and if the beatis not a noise beat, the presence of PNS is evaluated for the beat basedon the PNS test signals to determine whether the beat is a PNS beat. Ifthe beat is both determined not to be associated with noise, and to be aPNS beat, the device determines whether PNS episode detection criteriahave been met. The determination whether PNS episode detection criteriahave been met may be based on a specific number or sequence of PNS beatsbeing detected. For example, PNS episode detection criteria may be metif a predetermined number of consecutive beats, such as three beats forexample, are identified on a beat-by-beat basis as PNS beats. Accordingto another example, PNS episode detection criteria may be met if PNS isdetected for every predetermined sequential beat for a total number ofbeats, such as for every third beat for three total beats, i.e.,beat(i), beat (i-3), beat (i-6), for example. Once the PNS episodedetection criteria are met, and therefore a PNS episode is detected,Block 312, the device may generate an alert, adjust the pacing vectorfor delivery of the pacing therapy, or suspend delivery of the pacingtherapy. In one example, the device may suspend determining of a PNSepisode in response to a determination as to whether the PNS noisecriteria and the PNS beat criteria having been performed for 11consecutive beats.

Therefore, in the example of FIG. 7, PNS test signal features within thenoise window are first evaluated for the beat to detect or determinewhether the beat is associated with noise. If noise is not detected forthe beat, the PNS test signal features within the PNS window areevaluated for the beat to detect or determine whether the beat isassociated with presence of PNS. If the beat is neither a noise beat nora PNS beat, the beat is classified as a non-PNS beat, and the processcontinues for the next beat identified by the PNS test signal until apredetermined number of beats have been evaluated, or a predeterminedtime period has expired. On the other hand, if the beat is notdetermined to be a noise beat and is determined to be a PNS beat, thebeat is classified as a PNS beat. In either case, i.e., the current beatbeing a PNS beat or not being a PNS beat, the process continues for thenext beat until either a predetermined number of beats have beenevaluated, a predetermined time period has expired, or a PNS episode isdetected based on a predetermined number or sequence of beats beingidentified, on a beat-by-beat basis, as PNS beats.

FIG. 8 is a graphical representation of determining of acousticartifacts of a heart sound signal for determining the presence ofphrenic nerve stimulation in a medical device, according to an exampleof the present disclosure. According to one example, the PNS test signalmay a heart sounds signal sensed by heart sounds sensor 82, and thepredetermined cardiac signal may be a Vp beat sensed by sensing module76. In other embodiments, the predetermined cardiac signal utilized maybe a right atrial pace (Ap) beat, or a right atrial sense (As) beat, forexample. In an example in which the PNS test signal is a heart soundssignal and the predetermined cardiac signal utilized is a Vp beat, thedevice, such as IMD 16, for example, or a device or monitoring systemexternal to IMD 16, determines the presence of a PNS episode usingacoustic artifacts of the heart sound signal that occur during a Vp beaton a beat-by-beat basis. The sensed heart sound signal data may bedigitized by a 16-bit ADC with ±64 mV range sampled at 256 Hz, andbandpass filtered. The absolute value of the filtered heart sound signal(|FHS|) is determined, and a predetermined number of beats are evaluatedfor PNS at a user selectable voltage and/or polarity.

In particular, as illustrated in FIG. 8, the device may determineacoustic artifacts from a sensed heart sounds signal 318 associated witha VP beat 320 and identifies a PNS window that includes apre-ventricular pace (PreVp) window 322 and a post ventricular pace(PostVp) window 326 for the Vp beat 320. According to another example,that includes detecting whether the current beat is a noise beat, inorder to determine acoustic artifacts from a sensed heart sounds signal318 associated with a VP beat, the device identifies a noise window 328for the beat 320, in addition to a PNS window that includes thepre-ventricular pace (PreVp) window 322 and the post ventricular pace(PostVp) window 326.

According to one example, the PreVp window 322 may extend to the beat320 from a point 324 along the heart sounds signal 318 that is apredetermined time period prior to the beat 320, such as an atrial pace(Ap) beat. Both the PostVp window 326 and the noise window 328 extendduring a predetermined time period of the heart sounds signal 318 afterthe beat 320, with the noise window extending beyond the PostVp window328. In one example, the PreVp window 322 may extend 25 samples (98 ms)prior to and including the beat 320, the Post Vp window 326 may extendfor the time period extending between 27 ms and 83 ms after the beat320, i.e., for the sample period between the 7^(th) sample and the 21stsample after the beat 320, and the noise window 328 may extend for thetime period extending between 27 ms and 313 ms after the beat 320, i.e.,for the sample period between the 7^(th) sample and the 80 sample afterthe beat 320. In another example, the Pre Vp window 322 may be less than25 samples before and including the beat 320 if either the pacedAV-delay (PAV) or the sensed AV-delay (SAV) is less than 25 samples. Inanother example, the Pre Vp window 322 may be 150 ms.

FIG. 9 is a flowchart of a method of determining the presence of phrenicnerve stimulation in a medical device, according to an example of thepresent disclosure. As illustrated in FIGS. 8 and 9, during detection ofphrenic nerve stimulation in an example in which the PNS test signal isa heart sounds signal and the predetermined cardiac signal is a Vp beat,the device senses the heart sounds signal 318 and determines heartsounds processing windows of the heart sounds signal 318 for a currentbeat, Block 340. For example, the device determines the heart soundsbased PNS window, i.e., PreVp window 322 and post Vp window 326, for thecurrent sensed Vp beat. Signal artifacts of the heart sounds signal,such as one or more of a maximum, a minimum, a range, a mean, a sum andan absolute difference are calculated within the heart sounds based PNSwindow. i.e., PreVp window 322 and PostVp window 326. Absolutedifference is analogous to standard deviation (SD) and is calculated bysubtracting the mean from a signal, summing the absolute value of theresulting time series and dividing by the length of the signal. Usingthe determined heart sounds signal artifacts, the device determineswhether PNS beat criteria are met for the beat. If the PNS beat criteriaare met, the beat is determined to be a PNS beat. On the other hand, ifthe PNS beat criteria are not met, the beat is not determined to be aPNS beat.

In order to determine whether the PNS beat criteria are met, the devicedetermines whether a maximum of the absolute value of the filtered heartsounds signal |FHS| within the postVp window 326 criteria and a sum ofthe absolute value of the filtered heart sounds signal |FHS| within thepostVp window 326 criteria are satisfied. For example, the device maydetermine whether the maximum of the absolute value of the filteredheart sounds signal |FHS| within the postVp window 326 is greater than aPNS maximum threshold, Block 342.

In one example, the PNS maximum threshold in Block 342 of FIG. 9 may beset as the sum of 3 times the mean of the absolute value of the filteredheart sounds signal |FHS| within the PreVp window 322 and two times thestandard deviation, i.e., the absolute difference, of the filtered heartsounds signal |FHS| within the PreVp window 322.

In another example, the PNS maximum threshold in Block 342 may be set asa variable PNS maximum threshold, a. For example, as illustrated belowin Table 1, the variable PNS maximum threshold a may be a function ofthe range of the filtered heart sounds signal FHS in the noise window328. For example, as shown in Table 1, the variable PNS maximumthreshold a may be set as 80 ADC units if the range of the filteredheart sounds signal FHS is less than 1070 ADC units, may be set as 500ADC units if the range of the filtered heart sounds signal FHS isbetween 1070 ADC units and 7000 ADC units, and may be set as 1800 ADCunits if the range of the filtered heart sounds signal FHS is greaterthan or equal to 7000 ADC units.

TABLE 1 Range of FHS α β <1070 80 250 1070 to <7000 350 1000 ≥7000 1800400

In another example, the device may determine that the maximum of theabsolute value of the filtered heart sounds signal |FHS| within thepostVp window 326 is greater than the PNS maximum threshold, Yes inBlock 342, if the absolute value of the filtered heart sounds signal|FHS| within the PostVp window 326 is determined both to be greater thanthe sum of 3 times the mean of the absolute value of the filtered heartsounds signal |FHS| within the PreVp window 322 and two times thestandard deviation of the filtered heart sounds signal |FHS| within thePreVp window 322, and greater than the variable PNS maximum threshold,α.

If the maximum of the absolute value of the filtered heart sounds signal|FHS| within the postVp window 326 is greater than the PNS maximum sumthreshold, YES in Block 342, the device determines whether the sum ofthe absolute value of the filtered heart sounds signal |FHS|within thepostVp window 326 is greater than a PNS sum threshold, Block 344. If thesum of the absolute value of the filtered heart sounds signal |FHS|within the postVp window 326 is greater than the variable PNS sumthreshold, YES in Block 344, the current beat is determined to be a PNSbeat, Block 346. On the other hand, if either the maximum of theabsolute value of the filtered heart sounds signal |FHS| within thepostVp window 326 is not greater than the PNS maximum sum threshold, Noin Block 342, or the sum of the absolute value of the filtered heartsounds signal |FHS| within the postVp window 326 is not greater than thePNS sum threshold, No in Block 344, the current Vp beat is determinednot to be a PNS beat, Block 348.

In one example the PNS sum threshold of Block 344 may be a sum of theabsolute value of the filtered heart sounds signal |FHS| within thePreVp window 322 and a PNS beat sum variable threshold, β. For example,as illustrated in Table 1, the variable PNS sum threshold β may be afunction of the range of the filtered heart sounds signal FHS in thenoise window 328. For example, as shown in Table 1, the variable PNS sumthreshold β may be set as 250 ADC units if the range of the filteredheart sounds signal FHS is less than 1070 ADC units, may be set as 1000ADC units if the range of the filtered heart sounds signal FHS isbetween 1070 ADC units and 7000 ADC units, and may be set as 400 ADCunits if the range of the filtered heart sounds signal FHS is greaterthan or equal to 7000 ADC units.

In another example, the PNS sum threshold of Block 344 may be a multipleof the sum of the absolute value of the filtered heart sounds signal|FHS| within the PreVp window 322, such as 1.25 times the sum ofabsolute value of the filtered heart sounds signal |FHS| within thePreVp window 322, for example. In one example, the device may determinethat the sum of the absolute value of the filtered heart sounds signal|FHS| within the PostVp window 326 is greater than the PNS sumthreshold, Yes in Block 344, if the absolute value of the filtered heartsounds signal |FHS| within the PostVp window 326 is determined to beboth greater than the sum of the absolute value of the filtered heartsounds signal |FHS| within the PreVp window 322 and the variable PNS sumthreshold β, and greater than the multiple of the sum of the absolutevalue of the filtered heart sounds signal |FHS| within the PreVp window322, i.e., 1.25 times the sum of the absolute value of the filteredheart sounds signal |FHS| within the PreVp window 322, for example.

Each time the current beat is identified as being a PNS beat, Block 346,the device determines whether PNS episode criteria have been satisfied,Block 352. If either the PNS episode criteria have not been satisfied,NO in Block 352, or the current Vp beat is determined not to be a PNSbeat, Block 348, the process continues with the next beat, Block 350, sothat once the determination of the whether a current beat 320 is a PNSbeat has been completed, the process is repeated for the next beat 330until a predetermined number of beats have been evaluated for thepresence of PNS. In one example, in order to ensure that the PNSevaluation is completed in less than 3 minutes at an estimated heartrate of 60 bpm for 16 vectors (11×16×1000 ms cycle length=176 s), up to11 beats may be evaluated for PNS at the user selectable voltage output.Therefore, the device may suspend determining of a PHS episode inresponse to the PNS criteria having been determined for 11 consecutivebeats without a PNS episode being detected.

If the PNS episode criteria have been satisfied, YES in Block 352, a PNSepisode is detected, Block 354. In one example, the PNS episode criteriaare determined to be satisfied, YES in Block 352, if a predeterminednumber of consecutive beats, such as three consecutive beats forexample, are identified, on a beat-by-beat basis, as PNS beats, andtherefore a PNS episode is detected, Block 354. In another example, thePNS episode criteria are determined to be satisfied, YES in Block 352,and therefore a PNS episode is detected, Block 354, if everypredetermined sequential beat is determined to be a PNS beat for a totalnumber of beats, such as every third beat for three total beats, i.e.,beat(i), beat (i-3), beat (i-6), for example, is determined to be a PNSbeat. Once a PNS episode is detected, Block 354, the device may storethe determination that a PNS episode was detected, generate an alert,adjust the pacing vector for delivery of the pacing therapy, or suspenddelivery of the pacing therapy.

FIG. 10 is a flowchart of a method of determining the presence ofphrenic nerve stimulation in a medical device, according to an exampleof the present disclosure. In certain instances, it may be desirable toensure that the determination of a beat being a PNS beat does not occuras a result of noise occurring in the test signal. For example, asillustrated in FIGS. 8 and 10, during detection of phrenic nervestimulation, the device senses the heart sounds signal 318 and indetermining heart sounds processing windows of the heart sounds signal318 for a current beat, Block 340, determines a heart sounds based noisewindow in addition to determining the heart sounds based PNS window,i.e., PreVp window 322 and PostVp window 326, described above. As aresult, signal features of the heart sounds signal, such as one or moreof a maximum, a minimum, a range, a mean, a sum and an absolutedifference are calculated within each of the heart sounds based noisewindow 328 and the heart sounds based PNS window. i.e., PreVp window 322and PostVp window 326. Absolute difference is analogous to standarddeviation (SD) and is calculated by subtracting the mean from a signal,summing the absolute value of the resulting time series and dividing bythe length of the signal. In the example of FIG. 10, the heart soundsignal features within the noise window 328 for the beat are firstevaluated to detect or determine whether the beat is associated withnoise. If noise is not detected for the beat, the heart sound signalfeatures within PreVp window 322 and PostVp window 326 for the beat arethen evaluated to detect or determine whether the beat is associatedwith the presence of PNS.

As illustrated in the example of FIG. 10, during the evaluation of thenoise window 328, the device determines whether a sum of the absolutevalue of the filtered heart sounds signal |FHS| within the noise window328 is greater than a noise sum threshold, Block 356. If the sum of theabsolute value of the filtered heart sounds signal |FHS| within thenoise window 328 is greater than the noise sum threshold, YES in Block356, the device determines whether a range (i.e., the difference betweenthe maximum and the minimum) of the filtered heart sounds signal FHS inthe noise window 328 is less than a noise range threshold, Block 358. Ifthe range of the filtered heart sounds signal FHS in the noise window328 is less than the noise range threshold, YES in Block 358, thecurrent beat is identified as a noise beat, Block 360, and the processcontinues with the next beat, Block 350.

If either the sum of the absolute value of the filtered heart soundssignal |FHS| within the noise window 328 is not greater than the noisesum threshold, NO in Block 356, or the range of the filtered heartsounds signal FHS in the noise window 328 is not less than the noiserange threshold, NO in Block 358, the device determines whether acombination of the sum of the absolute value of the filtered heartsounds signal |FHS| and the range of the filtered heart sounds signalFHS in the noise window 328 is greater than a combination threshold,Block 362. In one example, in order to determine whether the combinationis greater than the combination threshold in Block 362, the devicedetermines whether a product of the sum of the absolute value of thefiltered heart sounds signal |FHS| and the range of the filtered heartsounds signal FHS in the noise window 328 is greater than thecombination threshold.

If the sum of the absolute value of the filtered heart sounds signal|FHS| and the range of the filtered heart sounds signal FHS in the noisewindow 328 is greater than the combination threshold, YES in Block 362,the current beat is identified as a noise beat, Block 360, and theprocess continues with the next beat, Block 350. On the other hand, ifsum of the absolute value of the filtered heart sounds signal |FHS| andthe range of the filtered heart sounds signal FHS in the noise window328 is not greater than the combination threshold, NO in Block 362, thecurrent beat is identified as not being a noise beat, Block 364.According to one example, the noise sum threshold may be set as 22900ADC units, the noise range threshold may be set as 1000 ADC units, andthe combination threshold may be set as 170000000 ADC units squared ifthe combination is a product of the two thresholds.

In this way, a noise beat criteria for the current beat is met, and thebeat is determined to be a noise beat, Block 360, if both the sum of theabsolute value of the filtered heart sounds signal |FHS| within thenoise window 328 is greater than the noise sum threshold, YES in Block356, and the range of the filtered heart sounds signal FHS in the noisewindow 328 is less than the noise range threshold, YES in Block 358, orif the product of the sum of the absolute value of the filtered heartsounds signal |FHS| and the range of the filtered heart sounds signalFHS in the noise window 328 is greater than the combination threshold,YES in Block 362. On the other hand, the noise beat criteria for thecurrent beat are not met, and the beat is not determined to be a noisebeat, Block 364, if either the sum of the absolute value of the filteredheart sounds signal |FHS| within the noise window 328 is not greaterthan the noise sum threshold, NO in Block 356, or the range of thefiltered heart sounds signal FHS in the noise window 328 is not lessthan the noise range threshold, NO in Block 358, and the product of thesum of the absolute value of the filtered heart sounds signal |FHS| andthe range of the filtered heart sounds signal FHS in the noise window328 is not greater than the combination threshold, NO in Block 362.

When the noise beat criteria, Blocks 356, 358 and 362, for the currentbeat are not satisfied, and therefore the current beat is not determinedto be a noise beat, Block 364, the device determines whether PNS beatcriteria are met for the beat, using the method for such determinationas described above in FIG. 9, and the determination is not repeated herefor brevity sake. Each time the current beat is identified as being aPNS beat, Block 346, the device determines whether PNS episode criteriahave been satisfied, Block 352. If either the PNS episode criteria havenot been satisfied, NO in Block 352, or the current Vp beat isdetermined not to be a PNS beat, Block 348, the process continues withthe next beat, Block 350, so that once the determination of the whethera current beat 320 is a PNS beat has been completed, the process isrepeated for the next beat 330 until a predetermined number of beatshave been evaluated for the presence of PNS. In one example, in order toensure that the PNS evaluation is completed in less than 3 minutes at anestimated heart rate of 60 bpm for 16 vectors (11×16×1000 ms cyclelength=176 s), up to 11 beats may be evaluated for PNS at the userselectable voltage output. Therefore, the device may suspend determiningof a PHS episode in response to the PNS criteria having been determinedfor 11 consecutive beats without a PNS episode being detected.

If the PNS episode criteria have been satisfied, YES in Block 352, a PNSepisode is detected, Block 354. In one example, the PNS episode criteriaare determined to be satisfied, YES in Block 352, if a predeterminednumber of consecutive beats, such as three consecutive beats forexample, are identified, on a beat-by-beat basis, as PNS beats, andtherefore a PNS episode is detected, Block 354. In another example, thePNS episode criteria are determined to be satisfied, YES in Block 352,and therefore a PNS episode is detected, Block 354, if everypredetermined sequential beat is determined to be a PNS beat for a totalnumber of beats, such as every third beat for three total beats, i.e.,beat(i), beat (i-3), beat (i-6), for example, is determined to be a PNSbeat. Once a PNS episode is detected, Block 354, the device may storethe determination that a PNS episode was detected, generate an alert,adjust the pacing vector for delivery of the pacing therapy, or suspenddelivery of the pacing therapy.

PNS beat criteria and noise beat criteria for determining phrenic nervestimulation in a medical device according to one example of the presentdisclosure may be as summarized below:

-   -   Noise beat criteria=(A AND B) OR C        -   A: Sum of |FHS| in noise window >22900        -   B: Range of FHS in noise window <1000        -   C: A×B >170000000    -   PNS beat criteria 32 D AND E AND F AND G        -   D: Max of |FHS| in PostVp>3×Mean of |FHS| in PreVp+2×SD of            |FHS| in PreVp        -   E: Max of |FHS| in PostVp>α        -   F: Sum of |FHS| in PostVp>Sum of |FHS| in PreVp+β        -   G: Sum of |FHS| in PostVp>1.25×Sum of |FHS| in PreVp

In the example illustrated in FIG. 9, the device determines acousticartifacts of the sensed heart sounds signal within the pre-ventricularpaced (PreVP) window 322 and the post-ventricular (PostVP) window 326 ofthe heart sounds signal sensed during a ventricular paced beat 320delivered by the device. The device determines, in response to acousticartifacts of the sensed heart sounds signal within the pre-ventricularpaced (PreVP) window and the post-ventricular (PostVP) window, whetherPNS criteria have been satisfied. In response to the PNS criteria beingsatisfied, the device determines whether PNS episode criteria have beensatisfied, and detects a PNS episode in response to the PNS episodecriteria being satisfied. It is understood that while any combination ofPNS beat criteria D-G may be utilized to determine whether PNS beatcriteria have been satisfied, in one example the device may identify thecurrent beat as a PNS beat if the maximum of the |FHS| within the PostVpwindow is determined to be greater than the sum of 3 times the mean ofthe |FHS| within the PreVp window and two times the standard deviationof the |FHS| within the PreVp window (PNS Beat Criteria D), the maximumof the |FHS| within the PostVp window is determined to be greater than avariable PNS maximum threshold a (PNS Beat Criteria E), wherein thevariable PNS maximum threshold is a function of a range of the filteredheart sounds signal (FHS) in the noise window, the sum of the |FHS|within the PostVp window is determined to be greater than a sum of the|FHS| within the PreVp window and a variable PNS sum threshold β (PNSBeat Criteria F), wherein the variable PNS beat sum threshold is afunction of the range of the filtered heart sounds signal FHS in thenoise window, and the sum of the |FHS| within the PostVp window isdetermined to be greater than a multiple of the sum of the |FHS| withinthe PreVp window (PNS Beat Criteria F).

In the example illustrated in FIG. 10, the device determines acousticartifacts within each of the noise window 328, the pre-ventricular paced(PreVP) window 322 and the post-ventricular (PostVP) window 326 of theheart sounds signal sensed during a ventricular paced beat 320 deliveredby the device. The device determines, in response to acoustic artifactsof the sensed heart sounds signal within the noise window, whether noisecriteria have been satisfied, and determines, in response to acousticartifacts of the sensed heart sounds signal within the pre-ventricularpaced (PreVP) window and the post-ventricular (PostVP) window, whetherPNS criteria have been satisfied. In response to the PNS criteria beingsatisfied, the device determines whether PNS episode criteria have beensatisfied, and detects a PNS episode in response to the PNS episodecriteria being satisfied.

It is understood that while any combination of PNS Noise Beat CriteriaA-C may be utilized to determine whether PNS noise criteria have beensatisfied, in one example the device may identify the current beat as anoise beat in response to both the sum of the |FHS| within the noisewindow being greater than the noise sum threshold (PNS Noise BeatCriteria A) and the range of the FHS within the noise window being lessthan the noise range threshold (PNS Noise Beat Criteria B), or inresponse to a product of the sum of the |FHS| in the noise window andthe range of the FHS in the noise window being greater than acombination threshold (PNS Noise Beat Criteria C). In addition, thedevice identifies the current beat as not being a noise beat in responseto at least one of the sum of the |FHS| within the noise window notbeing greater than the noise sum threshold and the range of the FHSwithin the noise window not being less than the noise range threshold,and a product of the sum of the |FHS| in the noise window and the rangeof the FHS in the noise window not being greater than a combinationthreshold.

Techniques for detecting stimulation of one or more of phrenic nerves 36and 38 are primarily described herein as being performed by IMD 16,e.g., by a processor of IMD 16. In other examples, some or all of thefunctions ascribed to IMD 16 or a processor thereof may be performed byone or more other devices such as programmer 24, or a processor thereof.For example, IMD 16 may process cardiac and/or heart sound signals todetermine whether therapy should continue to be delivered based oncurrent parameters, or whether adjustments to the parameters should bemade, and control the parameters used by IMD 16 to deliver the therapy.Alternatively, programmer 24 may process cardiac and/or heart soundsignals received from IMD 16 to determine whether therapy shouldcontinue to be delivered based on current parameters or whetheradjustments to the parameters should be made, and control according towhat parameters IMD 16 delivers the therapy. Furthermore, althoughdescribed herein with respect to an IMD, in other examples, thetechniques described herein may be performed or implemented in anexternal medical device, which may be coupled to a patient viapercutaneous or transcutaneous leads. In some examples, variousfunctions of IMD 16 may be carried out by multiple IMDs in communicationwith one another.

Illustrative Embodiments

-   Embodiment 1: A method of detecting phrenic nerve stimulation (PNS)    in a cardiac medical device, comprising:    -   sensing a test signal, the test signal being sensitive to        contraction of a diaphragm of a patient;    -   determining signal artifacts of the test signal within each of a        first window of the test signal prior to a predetermined cardiac        signal and a second window of the test signal subsequent to the        predetermined cardiac signal;    -   determining, in response to signal artifacts of the test signal        within the first window and the second window, whether PNS beat        criteria have been satisfied;    -   determining, in response to the PNS beat criteria being        satisfied, whether PNS episode criteria have been satisfied; and    -   detecting a PNS episode in response to the PNS episode criteria        being satisfied.-   Embodiment 2: The method of embodiment 1, wherein the test signal    comprises one of an acoustic signal and an accelerometer signal.-   Embodiment 3: The method as in any one of embodiments 1-2, wherein    the predetermined cardiac signal comprises at least one of a    ventricular pace (Vp) beat, an atrial sense (As) beat, and an atrial    pace (Ap) beat.-   Embodiment 4: The method as in any one of embodiments 1-3, wherein    the test signal comprises a heart sounds signal, and wherein    determining whether PNS beat criteria have been satisfied comprises:    -   determining whether a maximum of the absolute value of the heart        sounds signal (|FHS|) within the second window is satisfied;    -   determining whether a sum of the |FHS| within the second window        is satisfied; and    -   determining PNS criteria have been satisfied in response to both        the maximum of the |FHS| within the second window and the sum of        the |FHS| within the second window being satisfied.-   Embodiment 5: The method of embodiment 4, further comprising    determining signal artifacts of the test signal within a third    window of the test signal subsequent to the predetermined cardiac    signal and different from the second window, wherein determining    whether the maximum of the |FHS| within the second window is    satisfied comprises:    -   determining whether the maximum of the |FHS| within the second        window is greater than the sum of 3 times the mean of the |FHS|        within the first window and two times the standard deviation of        the |FHS| within the first window; and    -   determining whether the maximum of the |FHS| within the second        window is greater than a variable PNS maximum threshold, wherein        the variable PNS maximum threshold is a function of a range of        the heart sounds signal (FHS) in the third window.-   Embodiment 6: The method of embodiment 5, wherein determining    whether the sum of the |FHS| within the second window is satisfied    comprises:    -   determining whether the sum of the |FHS| within the second        window is greater than a sum of the |FHS| within the first        window and a variable PNS sum threshold, wherein the variable        PNS beat sum threshold is a function of the range of the heart        sounds signal FHS in the third window; and    -   determining whether the sum of the |FHS| within the second        window is greater than a multiple of the sum of the |FHS| within        the first window.-   Embodiment 7: The method as in any one of embodiments 1-6, further    comprising:    -   determining signal artifacts of the test signal within a third        window of the test signal subsequent to the predetermined        cardiac signal and different from the second window; and    -   determining, in response to signal artifacts of the test signal        within the third window, whether noise criteria have been        satisfied.-   Embodiment 8: The method of embodiment 7, wherein determining    whether noise criteria have been satisfied comprises:    -   determining whether a sum of the absolute value of the heart        sounds signal (|FHS|) within the third window is greater than a        noise sum threshold;    -   determining whether a range of the heart sounds signal (FHS)        within the third window is less than a noise range threshold;        and    -   identifying the beat as a noise beat in response to both the sum        of the |FHS| within the third window being greater than the        noise sum threshold and the range of the FHS within the third        window being less than the noise range threshold.-   Embodiment 9: The method of embodiment 8, further comprising:    -   determining, in response to at least one of the sum of the |FHS|        within the third window not being greater than the noise sum        threshold and the range of the FHS within the third window not        being less than the noise range threshold, whether a product of        the sum of the |FHS| in the third window and the range of the        FHS in the third window is greater than a combination threshold;        and    -   identifying the predetermined cardiac signal as not being a        noise beat in response to the product of the sum of the |FHS|        and the range of the FHS in the third window not being greater        than the combination threshold.-   Embodiment 10: The method as in any one of embodiments 1-8, wherein    determining whether PNS episode criteria have been satisfied    comprises one of:    -   determining whether the PNS criteria are satisfied for a        predetermined number of consecutive beats, and    -   determining whether the PNS criteria are satisfied for each        predetermined sequential beat over a number of beats.

Embodiment 11: The method as in any one of embodiments 1-10, furthercomprising performing, in response to the PNS episode being detected,one of:

-   -   storing the determination that the PNS episode was detected,    -   generating an alert,    -   adjusting a pacing vector, and    -   suspending delivery of a pacing therapy.

-   Embodiment 12: A cardiac medical device, comprising:    -   a first sensor to sense a test signal, the test signal being        sensitive to contraction of a diaphragm of a patient;    -   a second sensor to sense a predetermined cardiac signal; and    -   a processor operably coupled to the first sensor and the second        sensor and configured to:        -   determine signal artifacts of the test signal within each of            a first window of the test signal prior to a predetermined            cardiac signal and a second window of the test signal            subsequent to the predetermined cardiac signal,        -   determine, in response to signal artifacts of the test            signal within the first window and the second window,            whether PNS beat criteria have been satisfied,        -   determine, in response to the PNS beat criteria being            satisfied, whether PNS episode criteria have been satisfied,            and        -   detect a PNS episode in response to the PNS episode criteria            being satisfied.

-   Embodiment 13: The device of embodiment 12, wherein the test signal    comprises one of an acoustic signal and an accelerometer signal.

-   Embodiment 14: The device as in any one of embodiments 12-13,    wherein the predetermined cardiac signal comprises at least one of a    ventricular pace (Vp) beat, an atrial sense (As) beat, and an atrial    pace (Ap) beat.

-   Embodiment 15: The device as in any one of embodiments 12-14,    wherein the test signal comprises a heart sounds signal, wherein, to    determine whether PNS beat criteria have been satisfied, the    processor is further configured to:    -   determine whether a maximum of the absolute value of the heart        sounds signal (|FHS|) within the second window is satisfied,    -   determine whether a sum of the |FHS| within the second window is        satisfied, and    -   determine PNS criteria have been satisfied in response to both        the maximum of the |FHS| within the second window and the sum of        the |FHS| within the second window being satisfied.

-   Embodiment 16: The device of embodiment 15, wherein the processor is    further configured to:    -   determine signal artifacts of the test signal within a third        window of the test signal subsequent to the predetermined        cardiac signal and different from the second window,    -   determine whether the maximum of the |FHS| within the second        window is greater than the sum of 3 times the mean of the |FHS|        within the first window and two times the standard deviation of        the |FHS| within the first window, and    -   determine whether the maximum of the |FHS| within the second        window is greater than a variable PNS maximum threshold, wherein        the variable PNS maximum threshold is a function of a range of        the heart sounds signal (FHS) in the third window.

-   Embodiment 17: The device of embodiment 16, wherein, to determine    whether a sum of the |FHS| within the second window is satisfied,    the processor is further configured to:    -   determine whether the sum of the |FHS| within the second window        is greater than a sum of the |FHS| within the first window and a        variable PNS sum threshold, wherein the variable PNS beat sum        threshold is a function of the range of the heart sounds signal        FHS in the third window, and    -   determine whether the sum of the |FHS| within the second window        is greater than a multiple of the sum of the |FHS| within the        first window.

-   Embodiment 18: The device as in any one of embodiments 12-17,    wherein the processor is further configured to:    -   determine signal artifacts of the test signal within a third        window of the test signal subsequent to the predetermined        cardiac signal and different from the second window, and    -   determine, in response to signal artifacts of the test signal        within the third window, whether noise criteria have been        satisfied.

-   Embodiment 19: The device of embodiment 18, wherein, to determine    whether noise criteria have been satisfied, the processor is further    configured to:    -   determine whether a sum of the absolute value of the heart        sounds signal (IFHSI) within the third window is greater than a        noise sum threshold,    -   determine whether a range of the heart sounds signal (FHS)        within the third window is less than a noise range threshold,        and    -   identify the predetermined cardiac signal as a noise beat in        response to both the sum of the |FHS| within the third window        being greater than the noise sum threshold and the range of the        FHS within the third window being less than the noise range        threshold.

-   Embodiment 20: The device of embodiment 19, wherein the processor is    further configured to:    -   determine, in response to at least one of the sum of the |FHS|        within the third window not being greater than the noise sum        threshold and the range of the FHS within the third window not        being less than the noise range threshold, whether a product of        the sum of the |FHS| in the third window and the range of the        FHS in the third window is greater than a combination threshold,        and    -   identify the predetermined cardiac signal as not being a noise        beat in response to the product of the sum of the |FHS| and the        range of the FHS in the third window not being greater than the        combination threshold.

-   Embodiment 21: The device as in any one of embodiments 12-20,    wherein the processor is further configured to determine one of:    -   whether the PNS criteria are satisfied for a predetermined        number of consecutive beats, and    -   whether the PNS criteria are satisfied for each predetermined        sequential beat over a number of beats.

-   Embodiment 22: The device as in any one of embodiments 12-21,    wherein the processor is configured to perform one of:    -   storing the determination that the PNS episode was detected,    -   generating an alert,    -   adjusting a pacing vector, and    -   suspending delivery of a pacing therapy by the device in        response to a PNS episode being detected.

-   Embodiment 23: A non-transitory computer readable medium storing    instructions which cause a cardiac medical device to perform a    method comprising:    -   sensing a test signal, the test signal being sensitive to        contraction of a diaphragm of a patient;    -   determining signal artifacts of the test signal within each of a        first window of the test signal prior to a predetermined cardiac        signal and a second window of the test signal subsequent to the        predetermined cardiac signal;    -   determining, in response to signal artifacts of the test signal        within the first window and the second window, whether PNS beat        criteria have been satisfied;    -   determining, in response to the PNS beat criteria being        satisfied, whether PNS episode criteria have been satisfied; and    -   detecting a PNS episode in response to the PNS episode criteria        being satisfied.

All references and publications cited herein are expressly incorporatedherein by reference in their entirety into this disclosure, except tothe extent they may directly contradict this disclosure. Illustrativeembodiments of this disclosure are discussed and reference has been madeto possible variations within the scope of this disclosure. These andother variations and modifications in the disclosure will be apparent tothose skilled in the art without departing from the scope of thedisclosure, and it should be understood that this disclosure is notlimited to the illustrative embodiments set forth herein. Accordingly,the disclosure is to be limited only by the claims provided below.

What is claimed:
 1. A method of detecting phrenic nerve stimulation(PNS) in a cardiac medical device, comprising: sensing a test signal,the test signal being sensitive to contraction of a diaphragm of apatient; determining signal artifacts of the test signal within each ofa first window of the test signal prior to a predetermined cardiacsignal and a second window of the test signal subsequent to thepredetermined cardiac signal; determining, in response to signalartifacts of the test signal within the first window and the secondwindow, whether PNS beat criteria have been satisfied; determining, inresponse to the PNS beat criteria being satisfied, whether PNS episodecriteria have been satisfied; and detecting a PNS episode in response tothe PNS episode criteria being satisfied.